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A potential therapeutic system for Alzheimer’s disease using adsorbents with alkyl ligands for removal of blood amyloid β

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Abstract

Amyloid beta proteins (Aβ) in the brain are the main cause of Alzheimer’s disease. Peripheral administration of Aβ-binding substances, which may act as a sink for Aβ from the brain, has been reported to reduce brain Aβ. We previously found C16-cellulose beads had high Aβ-removal activity in vitro. In this study, we investigated the optimum surface properties of adsorbents for removal of Aβ in vitro and in humans. Batch analysis was performed with porous cellulose beads or silica beads with or without 2–22 methylene groups. Aβ-removal activity of C16-cellulose beads increased with increasing alkyl chain length. In contrast, with cellulose the amount of Aβ removed by the silica beads decreased with increasing alkyl chain length. Cellulose beads with 16 or 22 methylene groups were best (over 99 % removal) among all the beads tested (p ≤ 0.01). The adsorbent surfaces were analyzed by near-infrared spectroscopy, which revealed that the optimum beads had a sufficiently hydrophobic surface with an appropriate amount of adsorbed water accessible on the surface. Aβ removal efficiency by C16-cellulose beads was investigated for 5 renal failure patients on hemodialysis, resulting in 51.1 ± 6.6 % for Aβ1–40 and 43.8 ± 4.5 % for Aβ1–42 (p ≤ 0.01). In conclusion, cellulose beads with 16 or 22 methylene groups and an appropriate amount of adsorbed water were the optimum Aβ adsorbents. The device with C16-cellulose beads had high Aβ removal activity in humans. These adsorbents might be useful for Alzheimer’s disease therapy.

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Acknowledgments

The authors sincerely thank Dr Shigenobu Nakamura for useful discussions. The authors also thank Mr Eiji Ogino and Ms Ai Yonezawa for providing several materials, and Ms Yukari Murata and Sachi Oguri for technical assistance. This work was partly supported by KAKENHI (20509008, 22500419 and 23500531) and the Smoking Research Foundation.

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Authors and Affiliations

  1. Faculty of Clinical Engineering, School of Health Science, Fujita Health University, 1-98 Kutsukake-cho, Toyoake, Aichi, 470-1101, Japan

    Kazunori Kawaguchi, Sigeru Nakai, Hideo Hori, Atsushi Ohashi, Yoshiyuki Hiki & Nobuya Kitaguchi

  2. Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Sakai, Osaka, Japan

    Masato Takeuchi & Hiromasa Yamagawa

  3. Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, Japan

    Kazutaka Murakami & Yukio Yuzawa

  4. Chiryu Clinic, Chiryu, Japan

    Nobuo Suzuki

  5. Kanayama Clinic, Nagoya, Japan

    Satoshi Sugiyama

Authors
  1. Kazunori Kawaguchi
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  2. Masato Takeuchi
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  3. Hiromasa Yamagawa
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  4. Kazutaka Murakami
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  5. Sigeru Nakai
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  6. Hideo Hori
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  7. Atsushi Ohashi
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  8. Yoshiyuki Hiki
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  9. Nobuo Suzuki
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  10. Satoshi Sugiyama
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  11. Yukio Yuzawa
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  12. Nobuya Kitaguchi
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Correspondence to Kazunori Kawaguchi or Nobuya Kitaguchi.

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Kawaguchi, K., Takeuchi, M., Yamagawa, H. et al. A potential therapeutic system for Alzheimer’s disease using adsorbents with alkyl ligands for removal of blood amyloid β. J Artif Organs 16, 211–217 (2013). https://doi.org/10.1007/s10047-012-0675-z

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  • DOI: https://doi.org/10.1007/s10047-012-0675-z

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